Abstract

BackgroundTamoxifen (TAM) and Toremifene (TOR), two kinds of selective estrogen receptor modulators (SERMs), have equal efficacy in breast cancer patients. However, TAM has been proved to affect serum lipid profiles and cause fatty liver disease. The study aimed to compare the effects of TAM and TOR on fatty liver development and lipid profiles.MethodsThis study performed a retrospective analysis of 308 SERMs-treated early breast cancer patients who were matched 1:1 based on propensity scores. The follow-up period was 3 years. The primary outcomes were fatty liver detected by ultrasonography or computed tomography (CT), variation in fibrosis indexes, and serum lipid profiles change.ResultsThe cumulative incidence rate of new-onset fatty liver was higher in the TAM group than in the TOR group (113.2 vs. 67.2 per 1000 person-years, p < 0.001), and more severe fatty livers occurred in the TAM group (25.5 vs. 7.5 per 1000 person-years, p = 0.003). According to the Kaplan-Meier curves, TAM significantly increased the risk of new-onset fatty liver (25.97% vs. 17.53%, p = 0.0243) and the severe fatty liver (5.84% vs. 1.95%, p = 0.0429). TOR decreased the risk of new-onset fatty liver by 45% (hazard ratio = 0.55, p = 0.020) and showed lower fibrotic burden, independent of obesity, lipid, and liver enzyme levels. TOR increased triglycerides less than TAM, and TOR increased high-density lipoprotein cholesterol, while TAM did the opposite. No significant differences in total cholesterol and low-density lipoprotein cholesterol are observed between the two groups.ConclusionsTAM treatment is significantly associated with more severe fatty liver disease and liver fibrosis, while TOR is associated with an overall improvement in lipid profiles, which supports continuous monitoring of liver imaging and serum lipid levels during SERM treatment.

Highlights

  • Tamoxifen (TAM) and Toremifene (TOR), two kinds of selective estrogen receptor modulators (SERMs), have equal efficacy in breast cancer patients

  • This retrospective propensity score-matched cohort study was performed to compare the effect of TAM and TOR on the risk of newly developed fatty liver and the change of serum lipid profiles

  • Regardless of fatty liver, high-density lipoprotein-cholesterol (HDL-C) of the TOR group was increased while that of the TAM group was decreased. In this retrospective study, we found that compared with TOR use, TAM use significantly increased the risk of new-onset fatty liver, as well as the risk of severe fatty liver, during a 3-year follow-up

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Summary

Introduction

Tamoxifen (TAM) and Toremifene (TOR), two kinds of selective estrogen receptor modulators (SERMs), have equal efficacy in breast cancer patients. Since endocrine therapy is currently recommended for 5–10 years, the side effects of long-term use of TAM and TOR need to be acknowledged These include the risk of endometrial cancer, venous thrombosis, fatty liver disease, lipid dysfunction, and interference with infant development and breastfeed [5,6,7]. There are no data regarding the comparisons of fatty liver and serum lipids abnormality caused by TOR and TAM with a large sample size in premenopausal breast cancer. This retrospective propensity score-matched cohort study was performed to compare the effect of TAM and TOR on the risk of newly developed fatty liver and the change of serum lipid profiles

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